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Anti-cancer effects of artesunate in a panel of chemoresistant neuroblastoma cell lines

Item Type:Article
Title:Anti-cancer effects of artesunate in a panel of chemoresistant neuroblastoma cell lines
Creators Name:Michaelis, M. and Kleinschmidt, M.C. and Barth, S. and Rothweiler, F. and Geiler, J. and Breitling, R. and Mayer, B. and Deubzer, H. and Witt, O. and Kreuter, J. and Doerr, H.W. and Cinatl, J. and Cinatl, J.
Abstract:Artemisinin derivatives are well-tolerated anti-malaria drugs that also exert anti-cancer activity. Here, we investigated artemisinin and its derivatives dihydroartemisinin and artesunate in a panel of chemosensitive and chemoresistant human neuroblastoma cells as well as in primary neuroblastoma cultures. Only dihydroartemisinin and artesunate affected neuroblastoma cell viability with artesunate being more active. Artesunate-induced apoptosis and reactive oxygen species in neuroblastoma cells. Of 16 cell lines and two primary cultures, only UKF-NB-3(r)CDDP(1000) showed low sensitivity to artesunate. Characteristic gene expression signatures based on a previous analysis of artesunate resistance in the NCI60 cell line panel clearly separated UKF-NB-3(r)CDDP(1000) from the other cell lines. l-Buthionine-S,R-sulfoximine, an inhibitor of GCL (glutamate-cysteine ligase), resensitised in part UKF-NB-3(r)CDDP(1000) cells to artesunate. This finding together with bioinformatic analysis of expression of genes involved in glutathione metabolism showed that this pathway is involved in artesunate resistance. These data indicate that neuroblastoma represents an artesunate-sensitive cancer entity and that artesunate is also effective in chemoresistant neuroblastoma cells.
Keywords:Neuroblastoma, Artesunate, Artemisinin, Chemoresistance, Cancer, Chemotherapy
Source:Biochemical Pharmacology
ISSN:0006-2952
Publisher:Elsevier / Pergamon (U.S.A.)
Volume:79
Number:2
Page Range:130-136
Date:15 January 2010
Official Publication:https://doi.org/10.1016/j.bcp.2009.08.013
PubMed:View item in PubMed

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